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Integrative Repair of Knee Articular Surface Defects with Tissue Engineered Cartilage
Kavita T. Vakharia, MD, MS, Tamara Pylawka, M.D., Gregory Lewis, Ph.D., Henry Donahue, Ph.D., J. Spence Reid, M.D., T. Shane Johnson, M.D..
Penn State Hershey Medical Center, Hershey, PA, USA.
BACKGROUND: Injuries to articular cartilage joint surfaces arise from either acute intra-articular fractures or repetitive trauma leading to debilitating post traumatic arthritis. Current repair techniques rely on scar tissue formation by microfracturing subchondral bone. This tissue is biomechanically inferior to normal hyaline cartilage, and integrates poorly with surrounding healthy tissues. This project aims to improve chondrocyte-based repair of articular defects using ear chondrocytes as a cell source in a large animal, porcine model. The primary outcome is to obtain the formation of new cartilage that is biomechanically stronger than the current treatment and to view its integration into surrounding chondrocytes as well as binding to subchondral bone.
METHODS: Twelve adult pigs (60-80lbs, mean age 6mo) had ear cartilage biopsies with chondrocyte extraction and proliferation. Surgical procedures conformed to IACUC guidelines. One randomized knee was then exposed surgically under general anesthesia, and 14mm punch defects were made through the cartilage. One defect served as the current treatment control with microfracturing performed, the second defect was a clinical control with a fibrin gel scaffold suspension, and the third had a chondrocyte and fibrin gel suspension. The knees were then harvested for histology and biomechanical indentation testing after an 8 week weight bearing period.
RESULTS: Gross appearance of the defects showed edge integration to be the best in the defects filled with the chondrocyte and fibrin glue suspension. This sample on histology showed a new band of cartilage formation, whereas no cartilage production was seen in the microfracture samples. The biomechanical results revealed the microfracture technique to be significantly inferior to normal cartilage. The chondrocyte samples showed no biomechanical difference when compared to normal cartilage.
CONCLUSIONS: This study characterized the interfaces and bonds formed between engineered cartilage and subchondral bone, as well as between engineered cartilage and native cartilage using biomechanical testing and histology. Furthermore, the data showed a trend for the neocartilage generated from ear chondrocytes to be mechanically similar to normal cartilage than tissue formed from current treatment options. This supports the use of non-articular chondrocytes in joint repair. This research provides the groundwork for further large-scale testing of autologous cell engineering and transplantation to provide adjuncts to reconstructive repair of the acute fracture or in treatment of chronic disease.
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